Universal Flu Vaccine Part 2
Optimizing Response in Patients and Timeline for Development of a Universal Flu Vaccine
March 13, 2013
In February’s edition of the journal CHEST, Dr. Margarita Gomez Lorenzo and Dr. Matthew Fenton from the National Institute of Allergy and Infectious Diseases, and National Institutes of Health, discuss the challenges and opportunities that exist with creation of a universal influenza vaccine, in their article Immunobiology of Influenza Vaccines.
We asked Dr. Gomez and Dr. Fenton to discuss their findings including optimizing response to vaccines in patients, and the timeline for a universal flu vaccine. Below is the second of our two-part interview.
Why do some individuals not develop optimal responses to influenza vaccines, and is there a good way to optimize their response?
Dr. Gomez Lorenzo: One of the most important vaccine response variables is that the vaccine actually covers the strains that are circulating during that season. There must be a match of the strains that are in the vaccine and the strains that are circulating that flu season.
There are other factors that may impact protection in vaccine recipients—people with underlying medical conditions, people who have different genetic backgrounds, and also age. Age is a very important factor in response to vaccines. There is a process called immunosenescence, which we believe starts at a much earlier age than someone might think. This may start well before the fourth decade of life. In this process, the immune system doesn’t work; it is not able to have the same level of recognizing vaccine antigens. The immunologic memory, or the capacity to quickly respond with the production of antibodies to certain strains that the person has been exposed to in the past is impaired. And also, what tends to happen in the elderly is that the markers that are usually used for measuring and assuming that the person is protected against the strain is the antibody titers that are HA protein of the vaccine virus are not really reliable. So, in general, the more of these antibody titers, the better level of protection. However, there are elderly subjects who have antibody levels that are considered protected than in younger populations, and they still come down with influenza, in spite of being vaccinated. So, there is one important advance in the area of immunosuppression, which is the use of antigens. And the MA59 is an antigen that has been used in the manufacturing process of influenza vaccines in Europe and other countries, not in the US, so far, that has improved the response to the influenza vaccine in the elderly. And there is another approval which is the production of vaccines with a higher amount of the vital HA protein, which actually has been found to boost sufficiently the immune system of the elderly, and has led to the development of protected responses in this population.
Dr. Fenton: Your readers might be interested in a study we performed in 2009 (Busse WW, Peters SP, Fenton MJ, et al. Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine. J Allergy Clin Immunol. 2011;127(1): 130-137), during the H1N1 pandemic, which we published it in 2010. The study looked across ages and severity in people with underlying asthma, and we asked the question: were there certain people in the asthmatic population who were more or less able to raise their protection against the flu following vaccination? And what we found turned out to be simple, but it is very illustrative. When you looked at the elderly with severe asthma, this was the only group that did not develop robust protection to the vaccine when delivered at standard doses. This was compared with adults and adolescents with severe or mild asthma. They all responded normally to the vaccine. The only group of non-responders were the elderly (greater than 65 y/o) with severe asthma. What we discovered with that group was if we doubled the initial vaccine dose, that was all that was needed to bring their responses up to normal. We didn’t need to do anything more than that. And surprisingly, that study had never been done before, even though there is a lot of concern for asthma being a risk factor for people who might contract influenza. So it goes to what Dr. Gomez was saying, we may benefit from a new adjuvant. But in some cases, simply raising the vaccine dose might be sufficient.
When do you think a universal flu vaccine could be widely available?
Dr. Gomez Lorenzo: The NIH projects that in the next few years, we will have a universal influenza vaccine developed. There is a need for conducting clinical trials first to look at efficacy of the vaccines to see if they would eventually become qualified to be approved.
Dr. Fenton: I think the timeline Dr. Gomez Lorenzo is talking about is the time in which we can hold in our hand a vaccine and say, “Here it is, a universal flu vaccine.” There are trials to be done before we even begin on all of the work to head toward FDA approval, which is the only point in which the public sees that vaccine become available. To bring something to approval would be several additional years on top of that.
It ties back to what I said earlier, how universal is universal? If I was a drug company trying to manufacture this based on say, a NIH discovery, I might market it as a somewhat narrow claim. Something that will protect against the most common seasonal flu, strains with an expected protection of 5 years. And they might run the clinical trials for those specific outcomes. But if you’re going to make a claim on a label that a vaccine provides protection for 5 years, you’re actually going to have to prove it first.
We might have the actual thing in the laboratory in 3 to 5 years, but then we nee to begin process of large clinical trials, and FDA approval.
Special thanks to Dr. Gomez Lorenzo and Dr. Fenton for their time and expertise. We’ll certainly keep tabs on their work and the evolution of influenza vaccinations.